Chandra P K, Biswas A, Datta S, Banerjee A, Panigrahi R, Chakrabarti S, De B K, Chakravarty R
ICMR Virus Unit, Kolkata, India.
J Viral Hepat. 2009 Oct;16(10):749-56. doi: 10.1111/j.1365-2893.2009.01129.x. Epub 2009 May 3.
Hepatitis B genotype D (HBV/D) is the most widespread genotype and exists as at least five subgenotypes (HBV/D1-D5). However, little is known about the association of virological characteristics with clinical differences among HBV/D subgenotypes. To investigate the virological characteristics of these subgenotypes and their clinical implications, we selected a cohort of 109 genotype D infected individuals from the state of West Bengal, India, including 68 HBsAg positive patients and 41 with occult HBV infection. Among the HBsAg positive subjects 28 had chronic hepatitis B virus infection, 40 were asymptomatic carriers based on clinical examination, liver function test and ultrasonograph results. Overall, HBV/D1 was found in 17%, HBV/D2 in 29%, HBV/D3 in 34% and HBV/D5 in 20% of the cases. HBV/D1 was significantly associated with chronic liver disease (P = 0.01), and in this subgenotype A1896 (PreC mutations) were most common. Although BCP mutations (A/C1753 and T1762/A1764) were found to be frequently associated with HBV/D2 (33% and 33%) and D5 (47% and 59%), no apparent clinical correlation was observed. On the other hand, occult HBV infection was significantly associated with HBV/D3 infection, along with low level of BCP and PreC mutations and several non-synonymous substitutions in the catalytic reverse transcriptase (RT) domain of polymerase gene. Similar nucleotide substitutions in the surface (S) gene region were observed from both northern and eastern Indian HBV/D3 isolates. In conclusion, HBV/D subgenotypes differ in their mutational patterns in the S, polymerase and the BCP/PreC regions that may influence their clinical outcomes.
乙型肝炎病毒D基因型（HBV/D）是分布最广泛的基因型，至少存在五个亚型（HBV/D1-D5）。然而，关于HBV/D亚型之间病毒学特征与临床差异的关联，我们知之甚少。为了研究这些亚型的病毒学特征及其临床意义，我们从印度西孟加拉邦选取了109名感染D基因型的个体组成队列，其中包括68名HBsAg阳性患者和41名隐匿性HBV感染患者。在HBsAg阳性受试者中，根据临床检查、肝功能测试和超声检查结果，28例为慢性乙型肝炎病毒感染，40例为无症状携带者。总体而言，17%的病例中发现HBV/D1，29%中发现HBV/D2，34%中发现HBV/D3，20%中发现HBV/D5。HBV/D1与慢性肝病显著相关（P = 0.01），在该亚型中A1896（前C区突变）最为常见。虽然发现BCP区突变（A/C1753和T1762/A1764）与HBV/D2（33%和33%）和D5（47%和59%）频繁相关，但未观察到明显的临床相关性。另一方面，隐匿性HBV感染与HBV/D3感染显著相关，同时BCP区和前C区突变水平较低，且在聚合酶基因的催化逆转录酶（RT）结构域有几个非同义替换。在印度北部和东部的HBV/D3分离株中，表面（S）基因区域观察到类似的核苷酸替换。总之，HBV/D亚型在S区、聚合酶区以及BCP/前C区的突变模式不同，这可能会影响它们的临床结局。
